Twins and the mystery of missing heritability: the contribution of gene–environment interactions


  • J. Kaprio

    Corresponding author
    1. Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland
    2. Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
    3. Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland
    • Correspondence: Jaakko Kaprio, MD, PhD, Department of Public Health, PO Box 41 (Mannerheimintie 172), University of Helsinki, FIN-00014 Helsinki, Finland.

      (fax: 358 9 191 27 600; e-mail:

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Since 2006, the advent of increasingly larger genome-wide association studies and their meta-analyses have led to numerous, replicated findings of genetic polymorphisms associated with many diseases and traits. Early studies suggested that the identified loci generally accounted for a small fraction of the genetic variance estimated from twin and family studies. This led to the concept of ‘missing heritability’. Here, the progress in accounting for a greater proportion of the variance is reviewed. In particular, gene–environment interactions can, for some traits and in certain circumstances, explain part of this missing heritability.